Abstract Clam gardens traditionally established and maintained by coastal Indigenous Peoples of northwest North America are habitat modifications that enhance intertidal clam productivity and therefore provide secure and reliable local food resources. In this study, transcriptomic and phenotypic responses of Pacific littleneck clams ( Leukoma staminea ) were investigated in relation to transplantation to either clam gardens or unmodified clam beaches and growth for 16 weeks. Sediment characteristics (e.g., grain-size, carbonate, and organic content) were also evaluated and considered in the response. Large differences in phenotypic and abiotic characteristics were observed among beaches but did not differ based on unmaintained clam garden presence. A de novo transcriptome for L. staminea containing 52,000 putative transcripts was assembled and used to identify differential expression in response to the clam gardens. This identified a relatively small effect, but found two transcripts that were differentially expressed in both the gill and digestive gland tissues. In addition, differential expression along survival gradients, as well a tissue-specific expression analysis provide insight into the characteristics of the transcriptome and its ecological associations of this non-model organism. Across the beaches, abiotic characteristics with negative effects on growth and/or survival included small rocks, very fine sand, silt, carbonate, and organic content, whereas positive effects were observed from coarse sand, sand and fine sand. In conclusion, here it was found that localized environmental factors are likely to have a greater influence on Pacific littleneck clam physiology, growth, and survival than the presence or absence of unmaintained clam gardens.