Hypoxic responses in Oncorhynchus mykiss involve angiogenesis, lipid, and lactate metabolism, which may be triggered by the cortisol stress response and epigenetic methylation.

The incidence of hypoxia in water bodies is increasing more rapidly than aquatic life can adapt. This study aimed to determine the effects of hypoxia on fish physiology, as well as protein expression through proteomics. To do this, 40 rainbow trout were divided into normoxic control (11.5 mg/L dissolved oxygen) and hypoxic treatment (5 mg/L dissolved oxygen) tanks for a period of 7 days. Fish were then anesthetized and blood was sampled. Fish were then euthanized and heart and liver samples were taken. Blood glucose, cortisol and lipid, body and liver mass, fork length, hematocrit and, blood cell counts and global heart methylation were measured. Red blood cell counts were significantly lower, while hematocrit and mean corpuscular volume were significantly higher in the hypoxic treatment. Global DNA methylation was significantly decreased in hypoxic heart tissue. Plasma cortisol and 18:1 monoacylglyerol increased, while 15:0-18:1 phosphatidylethanolamine, and 18:1 lysophosphatidylethanolamine decreased in plasma of rainbow trout under hypoxic conditions. Plasma proteomics revealed 70 significantly altered proteins (p < 0.05) in the hypoxia treatment (Data are available via ProteomeXchange with identifier PXD026589). Many of these molecular changes appear to be related to the observed increase in red blood cell volume and epigenetic modifications, as well as to angiogenesis, lipid, and glucose metabolism. This study highlights a range of cellular and molecular responses in the blood and plasma of freshwater fish that may be phenotypic adaptions to hypoxia, and that could aid in diagnosing the health status of wild fish populations using several, potential, discovered biomarkers.