Integrated physiological, transcriptomic, and metabolomic analyses provide new insights into hypoxia tolerance in...

Owing to natural or anthropogenic factors, dissolved oxygen (DO) levels in aquatic environments frequently experience drastic fluctuations. Because fish are directly exposed to aquatic environments, DO fluctuations can disrupt physiological homeostasis, thereby inhibiting growth, reducing disease resistance, and potentially leading to mortality. To alleviate economic losses caused by hypoxia in Larimichthys crocea farming, we bred a novel strain with enhanced hypoxia tolerance. To elucidate the mechanisms underlying this enhanced tolerance, we conducted physiological, transcriptomic, and metabolomic analyses of both the hypoxia-tolerant (T) and control (N) groups under hypoxic stress to identify differentially expressed genes and metabolites. GO and KEGG enrichment analyses revealed that the T group adopted a more effective strategy when confronted with low oxygen levels, primarily by promoting glycolysis and the TCA cycle and enhancing the biosynthesis of carbohydrates, amino acids, terpenoids, and N-glycans. By contrast, the N group exhibited a relatively weaker glycolytic flux under hypoxic stress, with significant suppression of the tricarboxylic acid cycle and biosynthesis of energy-related substances and a greater reliance on oxygen-dependent lipid metabolism pathways. Overall, multi-omics analysis revealed hypoxia-induced alterations in metabolites and genes, providing crucial insights into the hypoxia tolerance mechanism of the L. crocea and offering evidence supporting the improved hypoxia tolerance of the selected population.