Gill tissue homeostasis remodeling and metabolic reprogramming: Key mechanisms underlying high-temperature stress resistance in selectively bred rainbow trout

Frequent extreme high-temperature events have severely restricted the development of the cold-water rainbow trout ( Oncorhynchus mykiss ) aquaculture industry, yet the systemic tolerance mechanisms behind the selection of heat-tolerant strains remain elusive. In this study, a 28-day thermal stress challenge (14–28 °C) was performed on common rainbow trout (N trout) and family-selected heat-tolerant rainbow trout (T trout, F 2 generation). Integrated biochemical, histopathological, and transcriptomic-metabolomic analyses were conducted. The results indicated that T trout effectively delayed the collapse of the antioxidant defense system under high temperatures (with significantly higher SOD, CAT, and GSH activities and significantly lower lipid peroxidation product MDA, P < 0.01). Gill cell apoptosis rates were significantly reduced ( P < 0.05). At the extreme temperature of 28 °C, T trout exhibited prominent compensatory structural remodeling of the gills ( P < 0.01) and sustained blood glucose mobilization capacity, thereby avoiding the metabolic failure seen in N trout. Multi-omics analysis further revealed that, distinct from the endoplasmic reticulum stress and cell membrane damage observed in N trout, T trout maintained protein homeostasis, likely through the upregulation of heat shock proteins (e.g., hspa1s , hsp90 ). Moreover, T trout achieved efficient thermal adaptation through metabolic reprogramming (restructuring carbohydrate metabolic to support the glutathione antioxidant system, upregulating gpx4a , and accumulating CHAC) and adaptive regulation of membrane lipids (e.g., arachidonic acid and sphingolipid pathways). This study systematically clarifies the key mechanisms of high-temperature tolerance in selectively bred rainbow trout, providing a vital theoretical basis and candidate markers (e.g., hspa1s and gpx4a ) for molecular marker-assisted breeding of stress-resistant cold-water fish.