Synergistic effects of infectious haematopoietic necrosis virus and <scp><i>Flavobacterium psychrophilum</i></scp> co‐infection on the mortality and pathophysiology of masu salmon parr <scp><i>Oncorhynchus masou</i></scp>

Co-infection with infectious haematopoietic necrosis virus (IHNV) and Flavobacterium psychrophilum is increasing in prevalence in salmonid aquaculture, and this is accompanied by increased economic losses. The aim of this study was to investigate the synergistic effects of IHNV and F. psychrophilum co-infection on mortality and pathophysiology in masu salmon Oncorhynchus masou. We performed challenge experiments involving co-infection with these pathogens and analysed the proteomic profiles in the kidneys of deceased fish using liquid chromatography tandem mass spectrometry (LC-MS/MS). The onset of co-infectious disease started earlier, and the mortality rate was significantly higher (90%-100%) compared with single infection. Moreover, co-infected fish exhibited severe clinical signs, which were a combination of the clinical signs associated with each single pathogen. Proteomic analysis found that the innate immune response and metabolomic pathways involving pentose-phosphate, fructose and nucleotides were altered in deceased co-infected fish compared with mono-infected fish, and fructose metabolism and the pentose-phosphate cycle were activated in co-infected deceased fish. These findings highlight the need for more comprehensive preventive measures to reduce the risk of multiple pathogen infections and improve the management of co-infectious diseases.