Aquaculture provides sustainable production of food fish with high protein/low-saturated fat to satisfy increasing demand. Globally, efficient and environmentally sustainable aquaculture production systems are urgently required. Over two decades of selective breeding, our research resulted in development of a rainbow trout strain that grows as well on an all-plant (about 50% soy based products) protein diet as on a fishmeal-based diet, and grows much faster than non-selected trout. In aquaculture, infectious diseases are the primary cause of economic losses, leading to the loss of millions of pounds of cultured product. Disease outbreaks are recognized as a significant constraint on aquaculture production, affecting its economic development. Disease susceptibility in fish is affected by intrinsic (genetic) and extrinsic (water quality, rearing density, feed rate, diet) factors and their interactions. The aquatic environment harbors a complex and dynamic microbial community (microbiota) and is in continuous contact with fish. In addition to selection for growth on replacement diets, families are tested for resistance to infectious hematopoietic necrosis virus (IHNV) and Flavobacterium spp. Each year, controls and crosses are also generated utilizing fish from the selected lines and from non-selected control lines to verify differences related to dietary tolerance and utilization. The ARS/UI fish are likewise being raised commercially under large scale production and evaluations are taking place that compare the survival of our selected fish to other strains under production conditions. Currently, we are using 53% soy protein (35% SBM and 18% SPC) for our selected plant diet for ARS/UI fish (trout). However, we would like to optimize the SBM and SPC level in the diet of selected (ARS/UI) trout and commercial trout by considering growth, gut health and resistance against viral and bacterial disease. Overall, successful completion of this project will have a broad application to commercial fish selective breeding programs, leading to increased profitability for US soy producers and fish farmers. The overall goal for this research project then is to determine the molecular mechanisms behind enhanced non-specific resistance in rainbow trout, while also studying the underlying innate immune changes that occur through disease selection. Again, the price of feed and losses to disease are the highest production costs and, therefore, the ability to reliably convey elevated, persistent non-specific immunity to other strains and/or species would be of great advantage for all aquaculture producers.