The foodborne pathogen Listeria monocytogenes is able to survive and grow in ready-to-eat foods, in which it is likely to experience a number of environmental stresses due to refrigerated storage and the physicochemical properties of the food. Little is known about the specific molecular mechanisms underlying survival and growth of L. monocytogenes under different complex conditions on/in specific food matrices. Transcriptome sequencing (RNA-seq) was used to understand the transcriptional landscape of L. monocytogenes strain H7858 grown on cold smoked salmon (CSS; water phase salt, 4.65%; pH 6.1) relative to that in modified brain heart infusion broth (MBHIB; water phase salt, 4.65%; pH 6.1) at 7°C. Significant differential transcription of 149 genes was observed (false-discovery rate [FDR], <0.05; fold change, >2.5), and 88 and 61 genes were up-and downregulated, respectively, in H7858 grown on CSS relative to the genes in H7858 grown in MBHIB. In spite of these differences in transcriptomes under these two conditions, growth parameters for L. monocytogenes were not significantly different between CSS and MBHIB, indicating that the transcriptomic differences reflect how L. monocytogenes is able to facilitate growth under these different conditions. Differential expression analysis and Gene Ontology enrichment analysis indicated that genes encoding proteins involved in cobalamin biosynthesis as well as ethanolamine and 1,2-propanediol utilization have significantly higher transcript levels in H7858 grown on CSS than in that grown in MBHIB. Our data identify specific transcriptional profiles of L. monocytogenes growing on vacuum-packaged CSS, which may provide targets for the development of novel and improved strategies to control L. monocytogenes growth on this ready-to-eat food.L isteria monocytogenes is a psychrotolerant foodborne pathogen that causes a potentially severe disease, listeriosis. This pathogen is of particular concern to the ready-to-eat (RTE) meat and seafood industries due to its ability to grow at temperatures as low as Ϫ0.4°C and under conditions of salt content as high as 25% (at 4°C) (1-3). Cold smoked salmon (CSS), an RTE seafood, represents a typical food product that can support the growth of L. monocytogenes from low numbers to potentially hazardous levels (4-9). The heat treatment applied during processing of CSS is not sufficient to inactivate microbes present on the raw material, including L. monocytogenes (10, 11). In addition, RTE food products, including CSS, can be contaminated with L. monocytogenes from environmental sources in processing facilities (10-13). Importantly, typical product characteristics of CSS, including pH, water activity (a w ), salt, and phenolic components, do not seem to be sufficient to control the growth of L. monocytogenes if it is present (8, 9).With the aim of developing control strategies that prevent or reduce growth of this pathogen in RTE seafood products, there is a need for a better understanding of the mechanisms that L. monocytogenes uses to sur...