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Genetic adaptation to new environmental conditions, such as changing diets, has always played a key role in the evolution of animals. Fish, in particular, have a great genetic potential for adaptability to regional environmental demands. Feeding diets devoid of marine resources to carnivorous fish species is paramount to enable fully sustainable aquaculture and independence of capture fisheries. Therefore, novel sources of protein substituting fishmeal in fish feed are of increasing interest in aquaculture. However, the use of plant-based protein sources in the diet of carnivorous fish is in controversial discussion because of their association with several issues related to food conversion, growth rate, fish health and welfare effects. The current study aims at making use of the genetic variability of rainbow trout (Oncorhynchus mykiss) in order to gain new insights into their adaptability to innovative raw materials with a particular focus on the question of how the replacement of fishmeal by Arthospira platensisand Hermetia illucensin fish feed affects the intestinal health. Therefore, 20% fishmeal of the total composition was completely replaced in each case with Arthrospira platensisor Hermetia illucens. The results showed that the stress response, investigated by analysing the concentration of heat shock protein 70 in liver samples, proved to be at very low values for all investigated groups. A chronic stress exposure due to the supplementation could thus be excluded. Regarding growth, the genetic background played a decisive role. Despite morphological and histological changes in the anterior intestine of experimental feeding groups, no negative influence on growth could be detected. A significantly higher expression of occludin in the posterior intestine of the Arthrospiragroups with respect to the epithelial barrier was noted. Altogether, no signs of cell infiltration were detected in the intestines of the animals despite the Arthrospirafed groups and one Hermetiafed group showing partially significantly higher gene expressions according to IL1β, TNFα and singular antimicrobial peptides than fish from other feedings. Therefore, the current study reveals that supplementing the fishmeal portion of rainbow trout diets with Arthrospira platensisor Hermetia illucensdoes not negatively affect fish health and animal welfare.