The physiological contro l, and number, of antimicrobial peptides (AMPs) is not well understood in finfish . Based on the new rainbow trout genome assembly, we identified 6 new saposin-like AMP genes in rainbow trout. Pr otein sequence alignments and in silico modeling show that the proteins encoded by those genes belong to the Nk-lysin AMP sub-family (termed: Nkl 1, 2, 3, 4 and Nkl-like a & b). Transcriptomic data show that expression of nkl1-nkl4 mRNAs occurred in many tissues. By contrast, the nkl-like a & b mRNAs are mostly expressed in immune-related tissues. T he effects of various aquaculture stressors, and a disease challenge (F. psychrophilum ; Fp) in rainbow trout, were examined using RNA sequencing . A bundances of nkl1, nkl2, nkl4, and nkl-like a were downregulated by high-temperature and salinity stress, and nkl3 and nkl-like b were downregulated by high-temperature. In the Fp challenge study, abundances of nkl3, nkl4, nkl-like a and nkl-like b, were significantly affected by genetic line (resistant vs non-resistant) and treatment (PBS or Fp), which were further verified by qRT- PCR with spleen tissue sampled at 4 post-challenge time points (0 - 144 h). This work represents an initial characterization of these Nkl proteins in rainbow trout, with ongoing in vitro work to characterize how these AMPs affect flavobacterial pathogens, their biofilms, and survival and replication of novirhabdoviral pathogens . Understanding the distribution, regulation and bioactivity of these AMPs may enable rational design of approaches to reduce infectious disease in commercial aquaculture.