When you open an Excel file, this window should open on the screen.

Which option do you select. (Yours will be related to an Excel file, not a PDF file)

hello, you also might want to try to change the following preference: enter about:config into the firefox address bar (confirm the info message in case it shows up) & search for the preference named browser.download.manager.scanWhenDone. double-click it and change its value to false.

You can save the file in Excel under a different name and possibly in a different folder after having edited the file.
Firefox may set the file to read-only to prevent dataloss because Firefox might delete such a file without notice after you close the external program and your edits would get lost.

When you choose Open in the Open/Save/Cancel dialog, Firefox usually uses the Windows TEMP folder. It is safer as cor-el suggests to save the document somewhere else either before or after making your edits. (My understanding of Read Only in Microsoft Office is not that you can't edit, but that you cannot save over the original, so you need to use Save As to save your edits.)