Multi-omics analysis reveals hypoxia adaptation mechanisms in an anti-flowing F1 generation of large yellow croaker (Larimichthys crocea).

The large yellow croaker (Larimichthys crocea) is a cornerstone of China's mariculture. This study integrates transcriptomic, proteomic, and metabolomic analyses to determine hypoxia adaptation mechanisms in an anti-flowing F1 generation (FDTL) compared with non-selected (FDCL) counterparts under 24-h hypoxic stress (2.0 mg/L dissolved oxygen). FDTL exhibited higher survival (67% vs. 42%). Transcriptomic analysis identified 852 differentially expressed genes, with significant enriched pathways including hypoxia-inducible factor signaling, glycolysis/gluconeogenesis, and IL-17-mediated immunity. Metabolomic profiling revealed 463 differential metabolites, predominantly associated with glycerophospholipid metabolism, arachidonic acid metabolism, and VEGF signaling. Proteomic screening detected 388 differentially abundant proteins, uniquely enriched in the cytokine-cytokine receptor interaction pathway. Cross-omics integration uncovered 37 shared pathways, with VEGF, GnRH, and C-type lectin receptor signaling pathways being co-regulated at the transcriptomic-metabolomic level. Notably, Core glycolysis-related genes and hypoxia-inducible factor-associated genes were markedly downregulated. This study confirmed that the anti-flowing strain exhibits a lower oxygen threshold for metabolic reprogramming, enabling sustained aerobic metabolic homeostasis under reduced oxygen levels. The integration of immune regulation and angiogenesis establishes a multi-layered hypoxia resistance network, providing molecular targets for breeding stress-tolerant fish. These findings highlight the FDTL's superior adaptability to high-density offshore aquaculture and validate the effectiveness of targeted breeding strategies.