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Infectious diseases may contribute to declines in Fraser River Sockeye salmon (Oncorhynchus nerka) stocks, but a clear knowledge gap exists around which infectious agents and diseases are important. This study was conducted to: 1) determine the presence and prevalence of 46 infectious agents in juvenile Fraser River Sockeye salmon, and 2) evaluate spatial patterns in prevalence and burden over initial seaward migration, contrasting patterns between two years of average and poor productivity. In total, 2,006 out-migrating Sockeye salmon were collected from four regions along their migration trajectory in British Columbia, in 2012 and 2013. High-throughput microfluidics quantitative PCR was employed for simultaneous quantitation of 46 different infectious agents. Twenty-six agents were detected at least once, including nine with prevalence >5%. Candidatus Brachiomonas cysticola, Myxobolus arcticus, and Pacific salmon parvovirus were the most prevalent agents. Infectious agent diversity and burden increased consistently upon smolts entry into the ocean, but they did not substantially change afterwards. Notably, both freshwater- and saltwater-transmitted agents were more prevalent in 2013 than in 2012, leading to an overall higher infection burden in the first two sampling regions. A reduction in the prevalence of two agents, erythrocytic necrosis virus and Paranucleospora theridion, was observed between regions 2 and 3, which was speculated to be associated with mortality during the first month at sea. The most prevalent infectious agents were all naturally occurring. In a small number of samples (0.9%), seven agents were only …