Integrated Liver Transcriptomic and Proteomic Analysis Reveals Resistance Mechanisms Against Pseudomonas plecoglossicida in Larimichthys crocea

Visceral white-nodules disease (VWND), caused by Pseudomonas plecoglossicida, poses a severe threat to the large yellow croaker (Larimichthys crocea) aquaculture industry. Although breeding resistant strains is a promising strategy, the molecular basis of disease resistance in this host remains poorly understood. Here, 1500 fish were artificially infected, and extreme phenotypes (30 resistant, RL; 30 susceptible, SL) were selected based on survival time and liver pathogen load. Liver histopathology revealed that RL fish maintained intact architecture with only mild vacuolation, whereas SL fish exhibited widespread necrosis, inflammation, and hemosiderin deposition. Consistently, RL fish showed lower MDA levels and higher GSH-Px activity and TAC. Transcriptomic analysis identified 172 differentially expressed genes (DEGs): RL fish were characterized by upregulation of anti-inflammatory and tissue-protective genes (Epo, CAV3) and downregulation of pro-coagulant factors (PAI1, K1kb1). Proteomic analysis identified 111 differentially expressed proteins, with significantly enriched pathways including the peroxisome, pentose phosphate, and phagosome pathways. Integrated cross-omics analysis revealed eight co-enriched KEGG pathways; among them, arginine/proline metabolism, phagosome, oxidative phosphorylation, and focal adhesion were consistently upregulated in the RL group. These findings suggest that effective resistance to VWND in L. crocea may involve a coordinated, multi-layered defense program encompassing redox balance, regulated immune responses, metabolic reprogramming, and cellular homeostasis. Cross-omics-supported candidate factors (e.g., P4ha1, COX6B, RAB5A, CAV3) represent promising targets for functional validation via DNA-level experiments in independent sample sets, and the prominent enrichment of arginine-proline metabolism indicates a potential target for dietary intervention that merits further investigation.