Why is there a difference between file size on my PC and the same file in SynergyXR Manager?

The file size shown in Windows is the compressed file size. 
Eg. an .mp4 and .mov are both compressed video file formats. When playing a video (even on Windows) the file is uncompressed, and thereby taking up more memory (RAM) than the actual file size on your hard drive.
If an application uses more memory than available, the only course of action by the operating system is to immediately shut down the app. To avoid this, we continuously monitor memory consumption, so we can avoid loading the file if that would take us over the edge of available memory. So the number you see in SynergyXR Manager is our estimated on-device memory consumption – which will always be higher than the file size.
You will notice the same for all other types of content as well (images, pdf and 3D models).