Fish Stress Physiology: Cortisol and the Stress Response

The physiology behind fish stress: the hormone cascade that releases cortisol, primary, secondary and tertiary responses, how cortisol suppresses immunity, and why handling and transport matter.

Stress as a physiological state

In fish-health extension literature, stress is described as a condition in which an animal cannot keep a normal physiological state because something is acting against its well-being. Stressors are often grouped into chemical stressors (poor water quality, pollution, diet composition, accumulated ammonia, nitrite or nitrate), biological stressors (crowding, aggression and territorial behaviour, pathogens and parasites), physical stressors (temperature, light, sound, dissolved gases) and procedural stressors (handling, shipping, disease treatments). The general husbandry side is covered in the stress-in-fish guide. This article focuses on the hormones and the physiology.

The hormone cascade that releases cortisol

Cortisol is the main glucocorticoid released during the stress response in most fish. The cascade starts in the brain. The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH acts on the melanocortin 2 receptor of the interrenal tissue, the fish equivalent of the adrenal cortex, which then makes and releases cortisol. In target tissues, cortisol binds glucocorticoid and mineralocorticoid receptors and changes gene expression. It also has faster non-genomic effects. Alongside cortisol, the nervous system releases the catecholamines adrenaline and noradrenaline. Apart from its role in stress, cortisol also regulates metabolism and osmoregulation in fish.

Primary, secondary and tertiary responses

Primary response: endocrine changes, mainly a rise in catecholamines and corticosteroids such as cortisol.
Secondary response: metabolic and physiological changes caused by those hormones. These include higher blood glucose and lactate, shifts in water and mineral balance, and changes in cardiovascular, respiratory and immune function. Heat-shock protein production rises and antibody production changes. Extension sources describe energy mobilisation from liver glycogen and fat, a faster heart rate and breathing, higher blood pressure and the release of reserve red blood cells.
Tertiary response: effects on the whole animal, such as slower growth, lower disease resistance, altered behaviour and reduced reproduction.

These responses help a fish escape or survive a threat in the short term, but they cost long-term maintenance, growth and reproduction. Extension sources also describe a classic sequence of alarm, resistance and exhaustion. During resistance, the fish can look and behave normally while it uses up its energy reserves. Exhaustion follows when the stressor is too strong or lasts too long.

What cortisol numbers look like

Cortisol values depend strongly on the species, the sampling method and the laboratory assay, so there is no universal normal range. A 2023 systematic review and meta-analysis of European sea bass (Dicentrarchus labrax), a species known for high and very variable cortisol, gives pooled plasma levels of 88.7 ng/mL at baseline (57 data sets) and 385.9 ng/mL after acute stress (34 data sets). In this species, cortisol starts to rise at least 6 minutes after a stressor and peaks about 60–120 minutes later, when recovery begins. The results differed between assay types, with immunoassays based on ELISA reading higher than radioimmunoassays, and with how the fish were anaesthetised or killed before blood sampling. Because of this, values from different studies cannot be compared directly.

Blood plasma shows the acute state, while mucus, faeces, scales and even the surrounding water can be used as less invasive samples. Scales build up cortisol over time and reflect chronic stress rather than a single event. Faecal cortisol lags behind the stressor by the gut transit time, which can range from under 30 minutes to more than 24 hours.

How stress weakens disease defences

Mucus: stress changes the chemistry of the slime layer, which contains enzymes (lysozymes) and antibodies. Handling also rubs mucus off. This weakens the chemical barrier and makes osmoregulation harder: freshwater fish take up too much water and marine fish lose it. Some stressed fish produce so much mucus that it smothers the gills and skin.
Skin and scales: injuries from nets, crowding or fighting open entry points for pathogens.
Inflammation: cortisol is anti-inflammatory and suppresses the non-specific immune response.
Specific immunity: stress hormones appear to interfere with the development of pathogen-specific receptors, so fewer antibodies are made. Prolonged stress severely limits immune effectiveness.
Temperature: rapid cooling slows immune processes, and cold stress can stop the activity of killer cells. Near a fish's upper thermal limit, immunity becomes impaired while pathogens keep growing.

Very young fish and spawning fish are especially likely to become infected after handling, because the immune system is still developing in juveniles and some reproductive hormones suppress it.

Handling and transport stress

Netting, handling and transport are short but severe stressors. Aquaculture best-management guidance aimed at reducing their impact includes the following points.

Use knitted-mesh rather than knotted nets to reduce injury and scale loss, and lower the water level to avoid long chases.
Take fish out of water as few times as possible, and work quickly and gently.
Keep temperature stable during transport, or change it very slowly when acclimating.
Keep oxygen adequate in transport and holding containers, and aerate immediately after capture.
For freshwater fish, the same guidance mentions adding 1.0–3.0 ppt salt to transport water to limit stress-induced osmotic imbalance. Marine species may benefit from slightly lower salinity in transport water. For long procedures it suggests an approved anaesthetic, noting that food fish may require a withdrawal period.