In some salmonid populations, multiple smolt age classes co-emigrate owing to variation in the duration of freshwater residence. While it is assumed that smolts prolong freshwater residence to maximize survival, infectious agent profiles and host gene expression (GE) have not been compared between concurrently migrating age classes. We coupled molecular assays of gill samples from nonlethally biopsied Chilko Lake sockeye salmon smolts with acoustic telemetry to study variation in infectious agent profiles and GE between age classes and survival groups. Although neither infectious agent profiles or GE were associated with survival, age-2 smolts exhibited higher mortality in the first 14 km of the downstream migration. There were measurable differences between the age classes in GE and the prevalence and load of “Candidatus Branchiomonas cysticola”, a bacterium commonly found in British Columbia salmonids. Relative to age-1 smolts, age-2 smolts displayed elevated GE related to inflammation and a molecular-based mortality-related signature. Although not associated with migration failure in this study, these patterns of GE are suggestive of mortality and could have implications for smolt survival.