Hepatic immunometabolic reprogramming of Sebastes schlegelii in response to Photobacterium damselae subsp. piscicida infection: biochemical, transcriptomic and metabolomic analyses.

Photobacterium damselae subsp. piscicida (PDP) is a highly virulent pathogen causing substantial economic losses in marine aquaculture, yet the molecular mechanisms of host-pathogen interactions remain poorly understood. In this study, we established a PDP infection model in black rockfish S. schlegelii and systematically investigated hepatic immunometabolic responses through integrated histopathological examination, biochemical enzyme assays, and multi-omics analyses. Time-course analysis identified 24 h post-infection as a critical window for host immune activation, characterized by peak activities of innate immune effectors, metabolic enzymes, and antioxidant enzymes. Integrated transcriptomic and metabolomic profiling at this pivotal time point revealed extensive metabolic reprogramming centered on three interconnected pathways. Energy metabolic reprogramming was evidenced by enhanced glycolytic flux and glutamine-dependent TCA cycle anaplerosis, reflecting the classical Warburg effect. Glycerophospholipid metabolism was profoundly disrupted, characterized by decreased phosphatidylcholine and phosphatidylethanolamine, accumulation of lysophospholipid derivatives, and altered expression of key regulatory genes, compromising membrane integrity while generating damage-associated molecular patterns that initiate innate immune signaling. Amino acid metabolism was extensively reprogrammed, with significant depletion of L-glutamine, L-cysteine, L-arginine, and multiple functional dipeptides, reflecting both host immune utilization and pathogen nutrient sequestration, which exacerbated oxidative damage. These immunometabolic events drive dual outcomes, namely the initiation of anti-infective immune defense and progressive liver injury. This integrated model identifies key metabolic nodes as potential therapeutic targets, providing a theoretical foundation for developing disease control strategies against bacterial septicemia in marine aquaculture.