The X-disease phytoplasma (‘Candidatus Phytoplasma pruni’) is an obligate pathogen that is capable of infection, persistence, and pathogenicity in both its major plant host (Prunus spp.) and leafhopper vector (Colladonus spp.) species. How the ‘Ca. P. pruni’ interacts with its plant and insect hosts, and how it alters its gene expression to do so is unknown, therefore in this study we conducted comparative RNAseq and differential gene expression analysis on ‘Ca. P. pruni’ infected P. avium and C. reductus samples. We found that the phytoplasma altered expression of approximately 32% of its annotated protein coding and pseudogenes, including intercellular transporters, proteolytic activity, its membrane structure, as well as upregulating genes associated with potential mobile units when in insect tissues vs. in plant tissues. Most notably, differential expression was observed in genes that were identified by in silico analysis as being putative secreted effectors that may play a role in allowing phytoplasma infection and survival in these two very different host systems, as well as inducing X-disease in Prunus spp., and offers targets for control by of this damaging pathogen by disrupting phytoplasma-host interactions.