AbstractSpruce weevil (Pissodes strobi) is a significant pest of regenerating spruce (Picea) and pine (Pinus) forests in North America. Weevil larvae feed in the bark, phloem, cambium, and outer xylem of apical shoots, causing stunted growth or mortality of young trees. We identified and characterized constitutive and weevil‐induced patterns of Sitka spruce (Picea sitchensis) transcriptomes in weevil‐resistant (R) and susceptible (S) trees using RNA sequencing (RNA‐seq) and differential expression (DE) analyses. We developed a statistical model for the analysis of RNA‐seq data from treatment experiments with a 2 × 3 factorial design to differentiate insect‐induced responses from the effects of mechanical damage. Across the different comparisons, we identified two major transcriptome contrasts: A large set of genes that was constitutively DE between R and S trees, and another set of genes that was DE in weevil‐induced S‐trees. The constitutive transcriptome unique to R trees appeared to be attuned to defense, while the constitutive transcriptome unique to S trees was enriched for growth‐related transcripts. Notably, a set of transcripts annotated as “fungal” was detected consistently in the transcriptomes. Fungal transcripts were identified as DE in the comparison of R and S trees and in the weevil‐affected DE transcriptome of S trees, suggesting a potential microbiome role in this conifer‐insect interaction.